Igor O. Nasonkin

Lineage Cell Therapeutics (United States)

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Ratnesh K. Singh

Lineage Cell Therapeutics (United States)

François Binette

Lineage Cell Therapeutics (United States)

Michael D. West

Craft Engineering Associates (United States)

Hal Sternberg

Lineage Cell Therapeutics (United States)

Sally A. Camper

University of Michigan–Ann Arbor

David LaRocca

Ithaca College

Karen Chapman

Eclipse Bioinnovations (United States)

Anand Swaroop

National Eye Institute

Ivan Labat

Lineage Cell Therapeutics (United States)

Simon M. Petersen‐Jones

Michigan State University

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University of Michigan–Ann Arbor

Johns Hopkins University

National Institutes of Health

Johns Hopkins Medicine

Michigan United

University of California System

Nanoprobes (United States)

University of Pittsburgh

Tokushima University

National Eye Institute

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Journal of Biological Chemistry (1999)

John D. Aitchison Akashi Tetsuyuki Yasmin Akbarali Alikasifoglu Ayfer Fiorella Altruda

10.1016/s0021-9258(19)51907-x

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Aged PROP1 Deficient Dwarf Mice Maintain ACTH Production

PLoS ONE (2011)

Igor O. Nasonkin R. DeC. Ward David L. Bavers Felix Beuschlein Amanda H. Mortensen

Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD) that typically advance from growth insufficiency diagnosed in infancy to include more severe growth hormone (GH) deficiency and progressive reduction in other anterior pituitary hormones, eventually including adrenocorticotropic hormone (ACTH) deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin, and thyroid stimulating hormone have been reported in the Prop1null (Prop1-/-) and the Ames dwarf (Prop1df/df) mouse models, but corticotroph and pituitary adrenal axis function have not been thoroughly investigated. Here we report that the C57BL6 background sensitizes mutants to a wasting phenotype that causes approximately one third to die precipitously between weaning and adulthood, while remaining homozygotes live with no signs of illness. The wasting phenotype is associated with severe hypoglycemia. Circulating ACTH and corticosterone levels are elevated in juvenile and aged Prop1 mutants, indicating activation of the pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are capable of responding to restraint stress with further elevation of ACTH and corticosterone. Low blood glucose, an expected side effect of GH deficiency, is likely responsible for the elevated corticosterone level. These studies suggest that the mouse model differs from the human patients who display progressive hormone loss and hypocortisolism.

Dwarfism

10.1371/journal.pone.0028355

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Citations (17)

Additional file 6: of Clonal derivation of white and brown adipocyte progenitor cell lines from human pluripotent stem cells

Figshare (2019)

Michael D. West Ching-Fang Chang David LaRocca Jie Li Jianjie Jiang

Table S3. Mitochondria quantitation data used in support of AdditionalÂ fileÂ 3: Figure S1 (sheet 1) and ELISA data used in support of Fig. 3b (sheet 2) are shown. (XLSX 16 kb)

Progenitor

White (mutation)

10.6084/m9.figshare.7559549

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Additional file 9: of Clonal derivation of white and brown adipocyte progenitor cell lines from human pluripotent stem cells

Figshare (2019)

Michael D. West Ching-Fang Chang David LaRocca Jie Li Jianjie Jiang

Table S6. A non-targeted relative quantitative liquid chromatographyâ tandem mass spectrometry RP and HILIC)/MS/MS platform was used to capture 624 cell metabolites and 406 metabolites in their respective media at time of harvest. Data is shown for fBAT and NP88 in undifferentiated and differentiated (in serum-free medium containing rosiglitazone, T3, and ITS for 14â days) cells. Data for other progenitor and adult cell lines is also presented in this table. (XLSX 474 kb)

White (mutation)

10.6084/m9.figshare.7559558

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Additional file 12: of Clonal derivation of white and brown adipocyte progenitor cell lines from human pluripotent stem cells

Figshare (2019)

Michael D. West Ching-Fang Chang David LaRocca Jie Li Jianjie Jiang

Table S5. Illumina-based microarray data is presented for the expression of Illumina-based microarray mean values and standard deviation for the genes FABP4, UCP1, ADIPOQ, CITED1, LIPASIN, MYH3, HOXA5, and DLX5 in fBAT, SAT, NP88, NP110, and nine new clonal isolates in the progenitor (Ctrl) state and after 14â days of differentiation in (BMP4, Rosi, T3, CL) in an effort to re-derive clonal progenitors to BAT. (XLSX 13 kb)

White (mutation)

Progenitor

10.6084/m9.figshare.7559531

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Long-Term, Stable Differentiation of Human Embryonic Stem Cell-Derived Neural Precursors Grafted into the Adult Mammalian Neostriatum

Stem Cells (2009)

Igor O. Nasonkin Vasiliki Mahairaki Leyan Xu Glen Hatfield B. Cummings

Abstract Stem cell grafts have been advocated as experimental treatments for neurological diseases by virtue of their ability to offer trophic support for injured neurons and, theoretically, to replace dead neurons. Human embryonic stem cells (HESCs) are a rich source of neural precursors (NPs) for grafting, but have been questioned for their tendency to form tumors. Here we studied the ability of HESC-derived NP grafts optimized for cell number and differentiation stage prior to transplantation, to survive and stably differentiate and integrate in the basal forebrain (neostriatum) of young adult nude rats over long periods of time (6 months). NPs were derived from adherent monolayer cultures of HESCs exposed to noggin. After transplantation, NPs showed a drastic reduction in mitotic activity and an avid differentiation into neurons that projected via major white matter tracts to a variety of forebrain targets. A third of NP-derived neurons expressed the basal forebrain-neostriatal marker dopamine-regulated and cyclic AMP-regulated phosphoprotein. Graft-derived neurons formed mature synapses with host postsynaptic structures, including dendrite shafts and spines. NPs inoculated in white matter tracts showed a tendency toward glial (primarily astrocytic) differentiation, whereas NPs inoculated in the ventricular epithelium persisted as nestin(+) precursors. Our findings demonstrate the long-term ability of noggin-derived human NPs to structurally integrate tumor-free into the mature mammalian forebrain, while maintaining some cell fate plasticity that is strongly influenced by particular central nervous system (CNS) niches.

Forebrain

Neuroblast

Nestin

10.1002/stem.177

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Citations (53)

THE SIXTH JOINT MEETING OF THE JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY AND THE U.S. HISTOCHEMICAL SOCIETY

ACTA HISTOCHEMICA ET CYTOCHEMICA (2002)

James F. Hainfeld Wenqiu Liu Vishwas N. Joshi Richard D. Powell Richard D. Powell

Heavy atom cluster complexes offer a number of advantages over conventional colloidal gold as labels, including chemically selective, site-specific conjugation to biological molecules, increased conjugate stability, and the capacity to make conjugates with a wide variety of molecules that cannot be directly labeled with colloidal gold.Using synthetic organic ligands, their surface properties may be tailored to minimize non-specific binding and aggregation.We have now applied these advantages, already well demonstrated with the 1.4 nm Nanogold cluster, to larger 3, 5 and 10 nm gold labels.Ligand-stabilized, functionalized 3, 5 and 10 nm gold particles have been prepared, isolated, and conjugated to antibodies and streptavidin.Conjugates were isolated chromatographically, and initial results in membrane blotting experiments indicate improved performance compared with equivalent colloidal gold probes.

Cytochemistry

10.1267/ahc.203-262

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Role of Epigenetics (DNA Methylation) in Retinal Differentiation

Investigative Ophthalmology & Visual Science (2009)

Igor O. Nasonkin D. Hambright Rivka A. Rachel Milan Jamrich Guillermo Oliver

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Derivation of retinal cells and retinal organoids from pluripotent stem cells for CRISPR-Cas9 engineering and retinal repair

Investigative Ophthalmology & Visual Science (2015)

Ratnesh K. Singh Ramya K. Mallela Pamela Cornuet Igor O. Nasonkin

Organoid

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Pluripotent Stem Cells for Retinal Tissue Engineering: Current Status and Future Prospects

Stem Cell Reviews and Reports (2018)

Ratnesh K. Singh Oscar Cuzzani François Binette Hal Sternberg Michael D. West

The retina is a very fine and layered neural tissue, which vitally depends on the preservation of cells, structure, connectivity and vasculature to maintain vision. There is an urgent need to find technical and biological solutions to major challenges associated with functional replacement of retinal cells. The major unmet challenges include generating sufficient numbers of specific cell types, achieving functional integration of transplanted cells, especially photoreceptors, and surgical delivery of retinal cells or tissue without triggering immune responses, inflammation and/or remodeling. The advances of regenerative medicine enabled generation of three-dimensional tissues (organoids), partially recreating the anatomical structure, biological complexity and physiology of several tissues, which are important targets for stem cell replacement therapies. Derivation of retinal tissue in a dish creates new opportunities for cell replacement therapies of blindness and addresses the need to preserve retinal architecture to restore vision. Retinal cell therapies aimed at preserving and improving vision have achieved many improvements in the past ten years. Retinal organoid technologies provide a number of solutions to technical and biological challenges associated with functional replacement of retinal cells to achieve long-term vision restoration. Our review summarizes the progress in cell therapies of retina, with focus on human pluripotent stem cell-derived retinal tissue, and critically evaluates the potential of retinal organoid approaches to solve a major unmet clinical need—retinal repair and vision restoration in conditions caused by retinal degeneration and traumatic ocular injuries. We also analyze obstacles in commercialization of retinal organoid technology for clinical application.

Regenerative Medicine

10.1007/s12015-018-9802-4

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Citations (61)